Pyridostigmine in Dysautonomia

Evidence-Based Recommendations by Condition

The American College of Cardiology recommends pyridostigmine as a second-line or adjunctive therapy for patients with neurogenic orthostatic hypotension who are refractory to other treatments, with a Class IIb, Level C-LD recommendation 1, 2, 3
Pyridostigmine may improve orthostatic tolerance through increases in peripheral vascular resistance and blood pressure by facilitating ganglionic cholinergic neurotransmission, and offers the advantage of not causing fluid retention or supine hypertension, unlike other agents used for orthostatic hypotension 2, 3, 4
The American College of Cardiology notes that while syncope occurs in POTS patients, it is relatively infrequent, and there is little evidence that syncope is directly due to POTS itself 1
Pyridostigmine is listed as a treatment option for nausea/vomiting and as a prokinetic agent in patients with hypermobile Ehlers-Danlos syndrome and comorbid POTS 5, 6

The American College of Cardiology suggests that patients should first optimize non-pharmacologic interventions, including increased salt and fluid intake, compression garments, physical counter-pressure maneuvers, and exercise training, before considering pyridostigmine 1, 2, 6

Common adverse effects of pyridostigmine include gastrointestinal problems, such as nausea, vomiting, and abdominal cramping, as well as cholinergic effects, such as sweating, salivation, and urinary incontinence 2, 3

The American College of Cardiology recommends trialing midodrine, droxidopa, or fludrocortisone before considering pyridostigmine for neurogenic orthostatic hypotension 1, 2
Pyridostigmine may be added when first-line agents are ineffective or poorly tolerated, supine hypertension limits use of other pressor agents, or fluid retention from fludrocortisone is problematic 1, 2, 4